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At least 37 records · Page 2

The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli

It is generally believed that mechanical signals must be large in order to be anabolic to bone tissue. Recent evidence indicates, however, that extremely low-magnitude (<10 microstrain) mechanical signals readily stimulate bone formation if induced at a high frequency. We examined the ability of extremely low-magnitude, high-frequency mechanical signals to restore anabolic bone cell activity inhibited by disuse. Adult female rats were randomly assigned to six groups: baseline control, age-matched control, mechanically stimulated for 10 min/day, disuse (hind limb suspension), disuse interrupted by 10 min/day of weight bearing, and disuse interrupted by 10 min/day of mechanical stimulation. After a 28 day protocol, bone formation rates (BFR) in the proximal tibia of mechanically stimulated rats increased compared with age-matched control (+97%). Disuse alone reduced BFR (-92%), a suppression only slightly curbed when disuse was interrupted by 10 min of weight bearing (-61%). In contrast, disuse interrupted by 10 min per day of low-level mechanical intervention normalized BFR to values seen in age-matched controls. This work indicates that this noninvasive, extremely low-level stimulus may provide an effective biomechanical intervention for the bone loss that plagues long-term space flight, bed rest, or immobilization caused by paralysis.

Non-NASA Center↗

Experiment K-314: Fetal and neonatal rat bone and joint development following in Utero spaceflight

Infant rat limb specimens from Soviet and U.S. ground-based studies were examined by radiography, macrophotography, histologic sectioning and staining and scanning electron microscopy. A comparison was conducted between vivarium and flight-type diets suggesting that nutritional obesity may adversely affect pregnancy. Data were obtained on maturation of ossification centers, orientation of collagen fibers in bone, tendon and ligaments, joint surface texture and spatial relationships of bones of the hind limb. Computer reconstructions of the knee and hip show promise as a means of investigating the etiology of congenital hip dislocation.

Sabelman, E. E.↗

Cement line staining in undecalcified thin sections of cortical bone

A technique for demonstrating cement lines in thin, undecalcified, transverse sections of cortical bone has been developed. Cortical bone samples are processed and embedded undecalcified in methyl methacrylate plastic. After sectioning at 3-5 microns, cross-sections are transferred to a glass slide and flattened for 10 min. Sections of cortical bone are stained for 20 sec free-floating in a fresh solution of 1% toluidine blue dissolved in 0.1% formic acid. The section is dehydrated in t-butyl alcohol, cleared in xylene, and mounted with Eukitt's medium. Reversal lines appear as thin, scalloped, dark blue lines against a light blue matrix, whereas bone formation arrest lines are thicker with a smooth contour. With this technique cellular detail, osteoid differentiation, and fluorochrome labels are retained. Results demonstrate the applicability of a one-step staining method for cement lines which will facilitate the assessment of bone remodeling activity in thin sections of undecalcified cortical bone.

NASA Discipline Number 40-99↗

Regeneration of critical-sized defects, in a goat model, using a dextrin-based hydrogel associated with granular synthetic bone substitute

Abstract The development of injectable bone substitutes (IBS) have obtained great importance in the bone regeneration field, as a strategy to reach hardly accessible defects using minimally invasive techniques and able to fit to irregular topographies. In this scenario, the association of injectable hydrogels and bone graft granules is emerging as a well-established trend. Particularly, in situ forming hydrogels have arisen as a new IBS generation. An in situ forming and injectable dextrin-based hydrogel (HG) was developed, aiming to act as a carrier of granular bone substitutes and bioactive agents. In this work, the HG was associated to a granular bone substitute (Bonelike®) and implanted in goat critical-sized calvarial defects (14 mm) for 3, 6 and 12 weeks. The results showed that HG improved the handling properties of the Bonelike® granules and did not affect its osteoconductive features, neither impairing the bone regeneration process. Human multipotent mesenchymal stromal cells from the umbilical cord, extracellular matrix hydrolysates and the pro-angiogenic peptide LLKKK18 were also combined with the IBS. These bioactive agents did not enhance the new bone formation significantly under the conditions tested, according to micro-computed tomography and histological analysis.

Pereira, Isabel↗

Development of a bone-fixation prosthetic attachment

An artificial limb attached directly to the bone by a quick-disconnect coupling was tested in-place at a California medical rehabilitation center. Its design concept and development, made possible by multiple spinoffs of aerospace technology, are discussed.

Owens, L. J.↗

Progress in Development of Methods in Bone Densitometry

The effects of weightlessness and decreased activity on the astronaut's musculoskeletal system during prolonged space flight, missions are of concern to NASA. This problem was anticipated from the knowledge that human subjects lose significant quantities of calcium from the skeleton during periods of bedrest, immobilization, and water immersion. An accurate method of measurement of the changes in mineral content of the skeleton is required not only in the space program but also in the biological, medical, and dental fields for mineral metabolism studies and for studying various pathological conditions of the skeleton and teeth. This method is a difficult one requiring the coordinated efforts of physiologists, biophysicists, radiologists, and clinicians. The densitometry methods reported in this conference which have been used or are being developed include X-ray, beta excited X-rays, radioisotopes, sonic vibration, and neutron activation analysis Studies in the Gemini, Biosatellite, and Apollo flights use the X-ray bone densitometry method which requires making X-rays before and after the flights. An in-flight method of bone densitometry would be valuable, and use of radioisotope sources has been suggested. Many advances in bone densitometry have been made in the last five years, and the urgency of the requirement makes this working conference timely and valuable. In such a rapidly developing field with investigators working independently in a variety of scientific disciplines, a working conference is of great value in exchanging information and ideas, critically evaluating approaches and methods, and pointing out new research pathways.

DENSITOMETER↗

Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

Bone Remodeling↗

Implementation and Integration of a Finite Element Model into the Bone Remodeling Model to Characterize Skeletal Loading

NASA's Digital Astronaut Project is developing a bone physiology model to predict changes in bone mineral density over the course of a space mission. The model intends to predict bone loss due to exposure in microgravity as well as predicting bone maintenance due to mechanical stimulus generated by exercise countermeasures. These predictions will be used to inform exercise device efficacy and to help design exercise protocols that will maintain bone mineral density during long exposures to microgravity during spaceflight. The mechanical stimulus and the stresses that are exhibited on the bone are important factors for bone remodeling. These stresses are dependent on the types of exercise that are performed and vary throughout the bone due to the geometry. A primary area of focus for bone health is the proximal femur. This location is critical in transmitting loads between the upper and lower body and have been known to be a critical failure point in older individuals with conditions like osteoporosis.

bone mineral content↗

Evaluation of the effects of hypergravity exposure and caging restraint on bone mineralization in the Beagle by in vivo photon absorptiometry

Photon absorptiometry was used to evaluate bone mineral kinetics associated with normal development and the possible perturbations to bone development resulting from hypergravity exposure over a period of six months in developing Beagles. A series of seven measurements were performed at specific times with the first measurement prior to treatment and subsequent measurements at 2, 5, 9, 14, 20 and 26 weeks from the onset of the experiment. Four groups of six male Beagle pups, ranging in age from 85 to 92 days were studied. Two groups were chronically exposed to hypergravity treatments by centrifugation of 2.0 G (18.0 RPM, 11.7 ft radius) and 2.6 G (18.0 RPM, 19.8 ft radius) for the 26 week period. A third group of six dogs served as a caged control to evaluate possible changes due to confinement in small plexiglass cages similar to those of the centrifuge. Thus this control group was subjected to limited exercise due to caging restraint. The fourth group of animals was housed in open runs to allow exercise without the spatial confinement of the smaller plexiglass cages. Results show highly significant differences in body weight, bone length, increase in bone density of control group relative to other groups, and a decrease in bone mineral content in the two gravity treated groups.

Fisher, G. L.↗

Latent bone modelling for estimation of plutonium concentration in skeleton of former nuclear workers

Abstract The skeleton is a major plutonium retention site in the human body. Estimation of the total plutonium activity in the skeleton is a challenging problem. For most tissue donors at the United States Transuranium and Uranium Registries, a limited number of bone samples is available. The skeleton activity is calculated using plutonium activity concentration (Cskel) and skeleton weight. In this study, latent bone modelling was used to estimate Cskel from the limited number of analysed bone samples. Data from 13 non-osteoporotic whole-body donors were used to develop latent bone model (LBM) to estimate Cskel for seven cases with four to eight analysed bone samples. LBM predictions were compared to Cskel estimated using an arithmetic mean in terms of accuracy and precision. For the studied cases, LBM offered a significant reduction of uncertainty of Cskel estimate.

Environmental Sciences & Ecology↗

Class I and class II major histocompatibility molecules play a role in bone marrow-derived macrophage development

Class I and class II major histocompatibility complex (MHC) molecules play significant roles in T cell development and immune function. We show that MHCI- and MHCII-deficient mice have low numbers of macrophage precursors and circulating monocytes, as well as abnormal bone marrow cell colony-stimulating factor type 1 secretion and bone composition. We suggest that MHCI and MHCII molecules play a significant role in macrophage development.

Non-NASA Center↗

Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss

During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

Mulugeta, L.↗

The Effect of Spaceflight on Bone Cell Cultures

Understanding the response of bone to mechanical loading (unloading) is extremely important in defining the means of adaptation of the body to a variety of environmental conditions such as during heightened physical activity or in extended explorations of space or the sea floor. The mechanisms of the adaptive response of bone are not well defined, but undoubtedly they involve changes occurring at the cellular level of bone structure. This proposal has intended to examine the hypothesis that the loading (unloading) response of bone is mediated by specific cells through modifications of their activity cytoskeletal elements, and/or elaboration of their extracellular matrices. For this purpose, this laboratory has utilized the results of a number of previous studies defining molecular biological, biochemical, morphological, and ultrastructural events of the reproducible mineralization of a primary bone cell (osteoblast) culture system under normal loading (1G gravity level). These data and the culture system then were examined following the use of the cultures in two NASA shuttle flights, STS-59 and STS-63. The cells collected from each of the flights were compared to respective synchronous ground (1G) control cells examined as the flight samples were simultaneously analyzed and to other control cells maintained at 1G until the time of shuttle launch, at which point they were terminated and studied (defined as basal cells). Each of the cell cultures was assayed in terms of metabolic markers- gene expression; synthesis and secretion of collagen and non-collagenous proteins, including certain cytoskeletal components; assembly of collagen into macrostructural arrays- formation of mineral; and interaction of collagen and mineral crystals during calcification of the cultures. The work has utilized a combination of biochemical techniques (radiolabeling, electrophoresis, fluorography, Western and Northern Blotting, and light microscopic immunofluorescence) and structural methods (conventional and high voltage electron microscopy, inununocytochemistry, stereomicroscopy, and 3D image reconstruction). The studies have provided new knowledge of aspects of bone cell development and structural regulation, extracellular matrix assembly, and mineralization during spaceflight and under normal gravity. The information has contributed to insights into the means in general by which cells respond and adapt to different conditions of gravity (loading). The data may as well have suggested an underlying basis for the observed loss of bone by vertebrates, including man, in microgravity; and these scientific results may have implications for understanding bone loss following fracture healing and extended periods of inactivity such as during long-term bedrest.

Landis, William J.↗

Maturation of bone and dentin matrices in rats flown on the Soviet biosatellite Cosmos 1887

We have studied the chemistry, hydroxyapatite crystal size, and maturational changes in bone and dentin from rats exposed to microgravity for 12 days in a Soviet biosatellite (Cosmos 1887). Bone ash was reduced in vertebrae (L5) but not in the non-weight-bearing calvaria or mandibles. All tissues had a relatively normal percentage composition of Ca, P, and Mg. Nevertheless, flight rat calvaria and vertebral tissues tended to exhibit lower Ca/P and higher Ca/Mg ratios that any of their weight-matched controls groups, and gradient density analysis (calvaria) indicated a strong shift to the fractions lower specific gravity that was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in the mandibles of flight rats was preferentially altered in such a way as to reduce their size (C-axis dimension). But in the mandibular diastemal region devoid of muscle attachments, flight rat bone and dentin were normal with respect to the Ca, P, Mg, and Zn concentrations and Ca/P and Ca/Mg ratios of age-matched controls. These observations affirm the concept that while microgravity most adversely affects the maturation of newly formed matrix and mineral moieties in weight-bearing bone, such effects occur throughout the skeleton.

NASA Experiment Number COS 1887-33↗

Biomaterials and bone mechanotransduction

Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.

Review↗

Clinical Practice Guideline for Vitamin D

Vitamin D and its metabolites have clinical significance because they play a critical function in calcium homeostasis and bone metabolism. Although not all of the pathologic mechanisms have been adequately described, vitamin D insufficiency and deficiency, as measured by low levels of 25-OH vitamin D, are associated with a variety of clinical conditions including osteoporosis, falls and fractures in the elderly, decreased immune function, bone pain, and possibly colon cancer and cardiovascular health.2 Apart from inadequate dietary intake, patients may present with low levels of vitamin D if they receive inadequate sunlight. The astronaut population is potentially vulnerable to low levels of vitamin D for several reasons. Firstly, they may train for long periods in Star City, Russia, which by virtue of its northern latitude receives less sunlight in winter months. Secondly, astronauts are deprived of sunlight while aboard the International Space Station (ISS). In addition, ISS crew members are exposed to microgravity for prolonged durations and are likely to develop low bone mineral density despite the use of countermeasures. Therefore, closely monitoring and maintaining adequate vitamin D levels is important for the astronaut corps.

Tarver, William J.↗

X-Ray Fluorescence Microscopy: A Method of Measuring Ion Concentrations in the Ear

This technical note describes synchrotron x-ray fluorescence microscopy (XFM) as a method for measuring the concentrations of various elements in cross-sections of the ear at extremely high resolution. This method could be of great importance for addressing many open questions in hearing research. XFM uses synchrotron radiation to evoke emissions from many biologically relevant elements in the tissue. The intensity and wavelength of the emitted radiation provide a fingerprint of the tissue composition that can be used to measure the concentration of the elements in the sampled location. Here, we focus on energies that target biologically-relevant elements of the periodic table between magnesium and zinc. Since a highly focused x-ray beam is used, the spot size is well below 1 mu m and the samples can be scanned at a nanometer lateral resolution. This study shows that measurement of the concentrations of different elements is possible in a mid-modiolar cross-section of a mouse cochlea. Images are presented that indicate potassium and chloride "hot spots" in the spiral ligament and the spiral limbus, providing experimental evidence for the potassium recycling pathway and showing the cochlear structures involved. Scans of a section obtained from the incus, one of the middle ear ossicles, in a developing mouse have shown that zinc is not uniformly distributed This supports the hypothesis that zinc plays a special role in the process of ossification. Although limited by sophisticated sample preparation and sectioning, the method provides ample exciting opportunities, to understand the role of genetics and epigenetics on hearing mechanisms in ontogeny and phylogeny.

59 BASIC BIOLOGICAL SCIENCES↗